Cuvette-Based Apparatus for Blood Coagulation Measurement and Testing

ABSTRACT

An apparatus for measuring blood clotting time includes a blood clot detection instrument and a cuvette for use with the blood clot detection instrument. The cuvette includes a blood sample receptor-inlet; a channel arrangement including at least one test channel for performing a blood clotting time measurement, a sampling channel having at least one surface portion that is hydrophilic, communicating with the blood sample receptor-inlet and the at least one test channel, and a waste channel having at least one surface portion that is hydrophilic, communicating with the sampling channel; and a vent opening communicating with the sampling channel. The sampling channel, the vent opening and the waste channel, coact to automatically draw a requisite volume of a blood sample deposited at the blood receptor-inlet, into the sampling channel.

RELATED APPLICATIONS

This application claims the benefit of U.S. Provisional Application No.61/081,290, filed Jul. 16, 2008, the entire disclosure of which isincorporated herein by reference.

FIELD

The invention relates to apparatus and methods for measuring and testingblood coagulation. More particularly, the invention relates to acuvette-based apparatus for blood coagulation measurement and testinghaving automatic volumetric blood sample filling capability.

BACKGROUND

Many people take anticoagulants to maintain the theropedic coagulationtime of their blood. Depending upon the person, the peak anticoagulanteffect of the anticoagulant may be delayed by many hours and/or days,and the duration of the effect may persist after the peak for anotherfour to five days. Accordingly, it is critical that the people who takeanticoagulants closely monitor the coagulation time of their blood, sothat they can monitor and adjust the amount of the anticoagulant theyare taking.

A common manner of determining the effective amount of anticoagulant ina person's blood is to perform a prothrombin time (PT) test. A PT testmeasures how long a sample of blood takes to clot. As a result, theanticoagulation or hemostasis level in the blood is directlyproportional to the length of time required to form clots.

Many devices and apparatus exist for performing coagulation timemeasurements and tests. Some of these apparatus are portable and simpleenough to operate by a person in his or her home. An example of such anapparatus is describe in U.S. Pat. No. 5,534,226, entitled PORTABLE TESTAPPARATUS AND ASSOCIATED METHOD OF PERFORMING A BLOOD COAGULATION TEST,issued to Gavin et al. and assigned to International TechnidyneCorporation, the assignee herein. The apparatus described in this patentincludes a disposable cuvette and a testing device. In operation, asample of blood is placed into a cup-like supply reservoir of thecuvette, the blood sample is drawn into the cuvette, and the coagulationtime of the blood sample is measured.

A problem associated with such apparatus, is that the volume of theblood sample drawn into the cuvette for measurement and testing iscontrolled by both the testing device and the sample cup removaltechniques. Moreover, the cup-like supply reservoir can be messy to use.

Accordingly, a need exits for an improved apparatus for measuring andtesting blood coagulation.

SUMMARY

A cuvette is described herein for use with a blood clot detectioninstrument. The cuvette comprises a blood sample receptor-inlet and achannel arrangement comprising: at least one test channel for performinga blood clotting time measurement; a sampling channel communicating withthe blood sample receptor-inlet and the at least one test channel; awaste channel communicating with the sampling channel; and a ventopening communicating with the sampling channel. At least the samplingchannel and the waste channel each has at least one surface portion, acoating, an insert or liner, and any combination thereof, that ishydrophilic. The sampling channel with its at least one surface portionthat is hydrophilic, the vent opening and the waste channel with its atleast one surface portion that is hydrophilic, coact to automaticallydraw a requisite volume of a blood sample deposited at the bloodreceptor-inlet, into the sampling channel. More specifically, aircompressed within the blood clot detection instrument, the at least onetest channel of the cuvette, and the section of the sampling channelextending beyond the vent opening of the cuvette, coacts with the wastechannel to cause the a leading edge of the blood sample drawn into thesampling channel from the blood receptor-inlet, to pull back within thesampling channel and uncover an optical sensor of the blood clotdetection instrument. The volume of the blood sample in the samplingchannel at the time when the blood sample is pulled back to uncover theoptical sensor, equals the requisite volume. The uncovering of theoptical sensor activates a pump module of the blood clot detectioninstrument, which draws the requisite volume of the blood sample intothe at least one test channel.

An apparatus is described herein for measuring blood clotting time. Theapparatus comprises: a blood clot detection instrument and a cuvette foruse with the blood clot detection instrument. The blood clot detectioninstrument comprises: a pump module and at least one pressure sensor.The cuvette comprises a blood sample receptor-inlet; a channelarrangement comprising: at least one test channel for performing a bloodclotting time measurement; a sampling channel communicating with theblood sample receptor-inlet and the at least one test channel; and awaste channel communicating with the sampling channel; and a ventopening communicating with the sampling channel. At least the samplingchannel has at least one surface portion, a coating, an insert or liner,and any combination thereof, that is hydrophilic. The sampling channelwith its at least one surface portion that is hydrophilic, the ventopening and the waste channel coact to automatically draw a requisitevolume of a blood sample deposited at the blood receptor-inlet, into thesampling channel, the requisite volume of blood sample being drawn intothe at least one test channel when the pump module of the blood clotdetection instrument is activated. The at least one test channel of thecuvette, and the pump module and the at least one pressure sensor of theclot detection instrument, coact to perform a blood clotting timemeasurement on the requisite volume of the blood sample.

Also described herein is a blood clot detection instrument forautomatically measuring blood clotting time of a blood sample containedin a test channel of a cuvette. The blood clot detection instrumentcomprises a pump module for communicating with the test channel of thecuvette; a pressure sensor; and a central processing unit. The centralprocessing unit executes instructions for operating the pump module in apressure alternating mode that pumps the blood sample back and forth ina test channel of a cuvette. During clot formation, the viscosity of theblood sample increases and causes a pumping pressure of the pump moduleto increase over time. The central processing unit executes furtherinstructions for obtaining a baseline pumping pressure from the pressuresensor upon initial operation of the pump module in the pressurealternating mode; obtaining additional pumping pressures over time fromthe pressure sensor; determining a pumping pressure difference valuebetween each additional pumping pressure and the baseline pumpingpressure; comparing each pumping pressure difference value to apredetermined threshold value; and indicating the blood clotting time ofthe blood sample when the pumping pressure difference value exceeds thepredetermined threshold value, the indicated blood clotting timecomprising a duration of time extending between the measurement of theadditional pumping pressure used for determining the pumping pressuredifference value that exceeded the predetermined threshold value and themeasurement of the baseline pumping pressure.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic view of an embodiment of a cuvette-based apparatusfor measuring blood coagulation or clotting time.

FIG. 2A is a schematic plan view of an embodiment of the disposablecuvette.

FIG. 2B is a sectional view through line 2B-2B of FIG. 2A.

FIG. 2C is a sectional view through line 2C-2C of FIG. 2A.

FIG. 3A is an enlarged view of a blood sample testing portion of thedisposable cuvette shown in FIG. 2A.

FIG. 3B is a section view through line 3B-3B of FIG. 3A.

FIG. 4 is an enlarged view of a volumetric blood sampling portion of thedisposable cuvette shown in FIG. 2A.

FIG. 5 is a pressure profile and clot detection graph.

FIG. 6A is a schematic plan view of another embodiment of the disposablecuvette.

FIG. 6B is a schematic plan view of a further embodiment of thedisposable cuvette.

FIG. 7A is a perspective view of a further embodiment of the disposablecuvette.

FIG. 7B is an enlarged view of encircled area 7B in FIG. 7A.

FIG. 7C is a sectional view through line 7C-7C in FIG. 7B.

Like reference numbers and designations in the various drawings indicatelike elements.

DETAILED DESCRIPTION OF THE INVENTION

Referring to FIG. 1, there is shown a schematic view of an embodiment ofa cuvette-based apparatus 10 for measuring blood coagulation or clottingtime. The apparatus 10 generally comprises a disposable cuvette 100 anda blood clot detection instrument 200. The apparatus 10 may be used formeasuring blood coagulation time by depositing a sample of blood (wholeblood or plasma) onto a specified location of the disposable cuvette 100and operatively coupling the disposable cuvette 100 to the clotdetection instrument 200. The cuvette 100 automatically selects or fillsitself with a requisite volume of the blood sample (to be tested)deposited at the specified location of the cuvette 100. The clotdetection instrument 200 facilitates automatic mixing of the bloodsample with a clotting reagent within the cuvette 100 and automaticallymeasures the clotting time of the selected volume of the blood samplemixed with the clotting reagent within the disposable cuvette 100,without contacting the blood sample. After completion of themeasurement, the cuvette 100 may be uncoupled or removed from the clotdetection instrument 200 and disposed of. Because the clot detectioninstrument 200 does not contact the blood sample, another cuvette 100may be operatively coupled to the clot detection instrument 200 formeasuring another blood sample without sterilization or other cleaningof the clot detection instrument 200.

Referring still to FIG. 1, the clot detection instrument 200 comprises apneumatic pump module 210, a motor 220 for driving the pump module 210,a plurality of tubes 230 extending from the pump module 210 forpneumatically coupling with the cuvette 100, a pressure sensor 240associated with each tube 230 for measuring the pneumatic pressurewithin the tube 230, and an optical sensor 250 for optically sensing asampling channel in the cuvette 100. In one embodiment, the opticalsensor 250 comprises, but is not limited, to a LED/photo sensor. Theclot detection instrument 200 also comprises, without limitation, acentral processing unit 260 (CPU) executing instructions for controllingthe operation of the motor 220 and thus the pump module 220 via signalsreceived from the optical sensor 250, and determining clotting timebased on the pressures sensed by the pressure sensors 240, a display(not shown) for displaying the measured clotting time or other datarelated to the measurement, a memory 270 for storing previouslyperformed measurements, and buttons, knobs, and/or switches (not shown)for operating the clot detection instrument 200, controlling the displayand/or accessing stored data from the memory 270.

Referring now to FIGS. 2A-2C, there is collectively shown a schematicplan view of an embodiment of the disposable cuvette 100. The cuvette100 comprises a substantially planar main body 110 defining generallyplanar top and bottom surfaces 111, 112. The cuvette main body 110 istypically made from a rigid, transparent hydrophobic or hydrophilicplastic material, using any suitable forming method, such molding. Theplastic hydrophobic materials may include, without limitationpolystyrene and polytetrafluoroethylene and the plastic hydrophilicmaterials may include, without limitation, styrene acrylonitrile,acrylonitrile styrene acrylate. The cuvette main body 110 may also bemade from other types of rigid, transparent hydrophobic or hydrophilicmaterials. The cuvette main body 110 includes an arrangement of openchannels formed in its bottom surface 112. The open channels are coveredand sealed by a thin, substrate 120 that is non-removably attached tothe bottom surface 112 of the cuvette body 110 When the cuvette mainbody 110 is not made from a hydrophilic material or is made from ahydrophobic material, the channels of the channel arrangement each haveat least one surface that is hydrophilic, and/or has a hydrophiliccoating, and/or has a hydrophilic insert disposed therein (formed, forexample, as a tube or liner, thereby fully or partially lining thechannel(s)), that facilitates the automatic filling function of thecuvette 100.

In one embodiment, at least a top surface 121 of the thin substrate 120,i.e., the surface in contact with the bottom surface 112 of the cuvettebody 110, is hydrophilic or has hydrophilic properties. The hydrophilicproperties of the top surface 121 of the substrate 120, facilitates therequisite volumetric selection of the blood sample deposited on thecuvette 100, for coagulation time measurement by the clot detectioninstrument 200. In other embodiments, requisite volumetric selection ofthe blood sample is accomplished by forming the cuvette body 110 from ahydrophilic material.

The thin substrate 120, in one embodiment, is a transparent film 122coated on one side with a layer 122 a of clear pressure sensitivehydrophilic adhesive. The layer 122 a of hydrophilic adhesive forms thetop surface 121 of the substrate 120 and non-removably attaches thesubstrate 120 to the bottom surface 112 of the cuvette body 110. Thetransparent film 122 may comprise, in one embodiment, a transparentpolyester material.

In an alternative embodiment the transparent film 122 is made from ahydrophilic material. Such a substrate may be attached to the bottomsurface 112 of the cuvette body 110 (with the top surface 121 of thesubstrate 120 mated with the bottom surface 112 of the cuvette body 110)with a layer of adhesive applied to the bottom surface 112 of cuvettebody 110. Alternatively, such a substrate may be attached to the bottomsurface 112 of the cuvette body 110 using heat sealing methods.

Referring still to FIGS. 2A-2C, the channel arrangement formed in thebottom surface of the cuvette body 110 generally comprises a samplingchannel 130, one or more test channels 140 and at least one wastechannel 150. A first end 131 of the sampling channel 130 communicateswith a sample depositing area 160 formed in a first or front end 113 ofthe cuvette body 110. The sample depositing area 160 in the front end113 of the cuvette body 110 and the exposed underlying portion of thesubstrate 120 form a blood sample receptor and inlet 161 (receptor-inlet161) on which the entire blood sample is deposited. The sampling channel130 extends longitudinally in the bottom surface of the cuvette body110, from the receptor-inlet 161, and merges at its second end with theone or more test channels 140 formed in the bottom surface of thecuvette body 110.

The channel arrangement shown in FIGS. 2A-2C further includes a jumperchannel 170 that branches off from the sampling channel 130 justdownstream of the receptor-inlet 161 and fluidly connects the wastechannel 150 with the sampling channel 130. The terminal end of the wastechannel 150 communicates with a waste channel venting aperture 151formed transversely through the cuvette body 110, which allows “dead”air displaced from within the waste and jumper channels 150, 170 byincoming blood, to be vented to the external environment. The wastechannel venting aperture 151 is open to the external environment at thetop surface 111 of the cuvette body 110 and closed by the substrate 120at the bottom surface of the cuvette body 110.

The channel arrangement shown in FIGS. 2A-2C further includes a ventchannel 180 that branches off from the sampling channel 130 downstreamof the jumper channel 170. The vent channel 180 communicates with a ventopening 181 formed transversely through the cuvette body 110 whichallows “dead” air displaced from within the sampling and vent channels130, 180 by incoming blood to be vented to the external environment. Thevent opening 181 is open to the external environment at the top surface111 of the cuvette body 110 and closed by the substrate 120 at thebottom surface of the cuvette body 110.

As shown in FIG. 2C, the sampling channel 130 (and the jumper, waste andvent channels 170, 150, 180) formed in the bottom surface 112 of thecuvette main body 110 has a smooth top T surface and smooth sidesurfaces S. The bottom surface B of the sampling channel 130 (and thejumper, waste and vent channels 170, 150, 180) is formed by the topsurface 121 (e.g., hydrophilic adhesive layer 122 a or the top surfaceof the hydrophilic film 122) of the substrate 120, which is also smooth.

The cuvette main body 110, in some embodiments, is made from ahydrophobic material. In such embodiments, the sampling, vent, jumper,and waste channels 130, 180, 170, and 150, respectively, each includesat least one surface that is hydrophilic, and/or has a hydrophiliccoating, and/or has a hydrophilic insert disposed therein, thatfacilitates the automatic sample sizing function of the cuvette 100.

In other embodiments, the cuvette main body 110 is made from ahydrophilic material. The one or more test channels 140 in suchembodiments, each includes at least one surface that is hydrophobic,and/or has a hydrophobic coating, and/or has a hydrophobic insertdisposed therein, where no automatic filling or sample sizing functionis required to be performed by the cuvette 100.

The requisite volume of blood sample selected by the cuvette 100 formeasurement by the clot detection instrument 200, is obtained from theblood sample deposited on the receptor-inlet 161. The size of thisvolume is determined by the effective volume of the sampling channel130. The effective volume of the sampling channel 130 is determined bythe width of the sampling channel 130, the height of the samplingchannel 130, and length of the sampling channel 130 as measured frompoint A, which is adjacent to the receptor-inlet 161, to point B, whichis adjacent to the vent channel 180. The jumper channel 170, connectingthe sampling channel 130 to waste channel 150, delays the filling of thewaste channel 150 until the sampling channel 130 is completely filled.The duration of the delay is controlled by an intersection I of thejumper channel 170 and the waste channel 150 and the length andcross-sectional area (CSA) of jumper channel 170 relative to the CSA ofthe waste channel 150, which insure that blood from the blood sampledeposited on the receptor-inlet 161, is drawn into the sampling channel130 prior to being drawn into the waste channel 150. The delay time isdetermined by the cross section area and length of the jumper channel170. The duration of the delay may be increased by lengthening thejumper channel 170, and/or decreasing the cross-sectional area (widthand height) of the jumper channel 170 relative to the CSA of the wastechannel to increase flow resistant through the jumper channel 170. Thus,during automatic blood sample volume sizing, the intersection I of thejumper channel 170 and the waste channel 150 acts like a resistor. Oncea blood sample is applied or deposited in the cuvette's receptor-inlet161, the blood sample enters the sampling channel 130 and the jumperchannel 170 substantially simultaneously. While the blood sample movesforward in the sampling channel 130, it also fills the jumper channel170, then stops at the intersection I of the jumper channel 170 and thewaste channel 150. The sampling channel 130 continues to fill until anequilibrium state is reached. The remaining sample in the receptor-inlet161 then forces the blood sample into the waste channel 150 from thejumper channel 170. The hydrophilic force of the waste channel 150 picksup and draws off the remaining blood sample in the receptor-inlet 161.

In one embodiment where the cuvette comprises three test channels 140,the sampling channel 130 has a width of about 0.055 inches, a height ofabout 0.014 inches, and a length of about 0.9 inches; the vent channel180 has a width of about 0.010 inches, a height of about 0.012 inches,and a length of about 0.140 inches; the jumper channel 170 has a widthof about 0.010 inches, a height of about 0.012 inches, and a length ofabout 0.25 inches; and the waste channel 150 has a width of about 0.066inches, a height of about 0.014 inches, and length of about 2.24 inches.The three test channels 140 of such a cuvette each has a width of about0.030 inches and a height of about 0.010 inches. The length of each ofthe outer two test channels is about 1.69 inches and the inner testchannel is about 1.634 inches. The sampling, jumper, waste, and testchannel(s) in other embodiments of the cuvette may have other suitabledimensions.

FIG. 6A shows an another embodiment of the cuvette, denoted by referencenumber 300. The cuvette 300 is substantially identical to the cuvette100 shown in FIG. 2A, except that the vent channel extending between thesampling channel and the vent opening is replaced by a vent opening 381that directly opens into the sampling channel 130.

FIG. 6B shows a further embodiment of the cuvette, denoted by referencenumber 400. The cuvette 400 is substantially identical to the cuvette100 shown in FIG. 2A, except that the waste channel 450 communicatesdirectly with the sampling channel 130 thereby omitting the jumperchannel. In addition, the waste channel 450 includes one or morerestrictions 452 located just after the entrance to the waste channel450 that function to delay filing of the waste channel 450.

FIGS. 7A-7C collectively show a further embodiment of a cuvette, denotedby reference number 500. The cuvette 500 is substantially identical tothe cuvette 100 shown in FIG. 2A, except that the one or more open testchannels 140 are formed in the top surface 111 of the main body 110instead of in the bottom surface 112 of the main body 110 where the opensampling, vent, jumper, and waste channels 130, 180, 170, 150 areformed. In addition, the open one or more test channels 140 in the topsurface 111 of the cuvette main body 110 are covered and sealed by athin substrate 530 with hydrophobic properties (e.g., the substrate 530includes a hydrophobic adhesive coating or is a hydrophobic film) thatis non-removably attached to the top surface 111 of the cuvette mainbody 110, and the open sampling, vent, jumper, and waste channels 130,180, 170, 150 in the bottom surface 112 of the cuvette main body 110 arecovered and sealed by a thin, substrate 520 with hydrophilic properties(e.g., the substrate 520 includes a hydrophilic adhesive coating or is ahydrophilic film) that is non-removably attached to the bottom surface112 of the cuvette body 110. As can be seen in FIGS. 7B and 7C, thesampling channel 103 and an inlet 540 to the one or more test channels140 are laterally offset from one another. A connecting channel 550formed in the top surface 111 of the cuvette main body 110, has a firstend 550 a that communicates with a terminal end of the sampling channel103 and a second end 550 b that communicates with an inlet 540 to theone or more test channels 140. The first end 550 a of the connectingchannel 550 is covered and sealed by the hydrophillic substrate 520. Theremainder of the connecting channel 550 including the second end 550 bthereof, is covered and sealed by the hydrophobic substrate 530. Theconnecting channel 550 transfers the volume of the blood sampleprecisely collected by the sampling channel 130, to the one or more testchannels 140.

In one embodiment, the one or more test channels 140 comprises abranched array of three test channels 140 in a menorah-shapedconfiguration 140 _(m) (visible in FIGS. 2A, 3A, 4, 6A and 6B). Themenorah-shaped array of test channels 140 _(m) evenly divides theselected volume of blood into three separate blood samples, therebyallowing the cuvette 100 to be used for performing up to three differentblood tests. For examples of the blood tests that may be performed inthe cuvette, see U.S. Pat. No. 5,534,226, entitled, PORTABLE TESTAPPARATUS AND ASSOCIATED METHOD OF PERFORMING A BLOOD COAGULATION TEST,assigned to the International Technidyne Corporation, the assigneeherein. The entire disclosure of U.S. Pat. No. 5,534,226 is incorporatedherein by reference. The branched array in other embodiments of thecuvette 100 may include two test channels 140 or more than three testchannels 140.

Referring still to FIGS. 2A, 3A, 4, 6A and 6B, the terminal or marginalterminal end of each test channel 140 communicates with a drive aperture141 formed through the cuvette body 110. The drive aperture 141 is opento the external environment at the top surface 112 of the cuvette body110 and closed by the substrate 120 at the bottom surface of the cuvettebody 110. When the cuvette 100 is operatively coupled to the clotdetection instrument 200, as shown in FIG. 1, the plurality of tubes 230extending from the pump module 210 sealingly engage the one or moredrive apertures 141 of the cuvette body 110, so that the arrangement ofchannels and the pneumatic pump module 210 of the clot detectioninstrument 200 form a pneumatic system when the cuvette 100 isoperatively coupled to the clot detection instrument 200.

Referring now to FIGS. 3A and 3B, each of the test channels 140 formedin the bottom surface of the cuvette body 110 includes end sections 142a with smooth top, side and bottom walls (the bottom wall of each testchannel 140 being formed by the smooth top surface 121 of the substrate120) similar to the top, side and bottom walls of the sampling, jumperand waste channels 130, 170, and 150, and an intermediate section 142 bwhere the top wall T_(T) and side walls S_(T) are textured. In onenon-limiting embodiment, the texturing may comprise a flat knurlcross-hatch. In other embodiments, the texturing in the intermediatesection 142 b of one or more of test channels 140 may only be on the topwall or on one or both of the side walls. The length of the texturedsection is selected so that the blood sample BLD always remains withinthis section of the test channel 140 during testing. A dehydrated clotpromoting reagent (not shown) for triggering and accelerating bloodclotting, is disposed in each test channel 140 where the texturing islocated. The reagent in each test channel 140 may be the same ordifferent. Therefore, in one embodiment, reagent A may be in each of thetest channels. In another embodiment, reagent A may be in two of thetest channels and reagent B may be in one of the test channels. In stillanother embodiment, reagent A may be in one of the test channels,reagent B may be in one of the test channels and reagent C may be in oneof the test channels. When the blood sample is drawn into the testchannels 140, the reagent rehydrates and mixes with the blood. Thetextured wall(s) of each test channel 140 improve reagent depositionthereon during manufacture of the cuvette, and increase clottingmeasurement sensitivity, as the blood sample is reciprocally moved oroscillated therein when measuring of the clotting time of the bloodsample, as will be explained further on. In an alternate embodiment, thetextured intermediate section of one or more the test channels 140 maybe replaced by a restricted area (not shown) where the test channel 140is narrowed.

The automatic volumetric filling function of the cuvette 100 will now bedescribed in greater detail with reference to FIG. 4. Prior tovolumetric filling, the cuvette 100 must be operatively coupled to theclot detection instrument 200 such that the plurality of tubes 230extending from the pump module 210 of the clot detection instrument 200sealingly engage the one or more drive apertures 141 of the cuvette body110, thereby creating a pneumatic system formed by the arrangement ofchannels of the cuvette 100 and the pneumatic pump module 210 of theclot detection instrument 200, as shown in FIG. 1. The automaticvolumetric filling function commences when a blood sample is depositedonto the receptor-inlet 161 of the cuvette 100. The blood sample may bedeposited on the receptor-inlet 161 by finger after a fingerstick, aneedle, a dropper, a pipette, a capillary tube, or any other suitabledepositing device. Since at least a portion of the sampling channel 130is hydrophilic, a force F_(s) is generated by the hydrophilicity of thisportion, which initially draws the blood sample deposited on thereceptor-inlet 161 into the sampling channel 130 until the entire ventchannel 180 becomes filled. The dead air in the vent channel 180 and thesection of the sampling channel 130 extending between the receptor-inlet161 and the vent channel 180, is vented through the vent opening 181 ofthe vent channel 180 as the blood BLD fills this section of the samplingchannel 130, and the vent channel 180. The blood drawn into the ventchannel 180 seals the vent opening 181. At the same time the jumperchannel hydrophilicity force F_(j) draws blood into the jumper channel.Once the vent channel 180 has been filled, the force F_(s) continues todraw more blood from the blood sample deposited on the receptor-inlet161 into the sampling channel 130 such that the blood BLD in thesampling channel 130 overshoots the vent channel 180 and covers theoptical sensor 250 of the clot detection instrument 200, which liesunder or over section or area 131 of the sampling channel 130. The bloodBLD which overshoots the vent channel 180 compresses the dead air volumecontained within the section of the sampling channel 130 extendingbeyond the vent channel 180, the test channels 140, and the tubes 230 ofthe clot detection instrument 200, and the pump module 210, becauseF_(s)>F_(p) and F_(w)<<F_(s), where F_(p) is the pressure of thecompressed dead air volume, and F_(w) is the hydrophilicity forcegenerated by at least a portion of the waste channel 150 that ishydrophilic. Blood stops flowing in the sampling channel 130 towards thetest channels 140 when an equilibrium state F_(s)=F_(p)+F_(w) isachieved therein.

After the equilibrium state has been reached, blood that has beendelayed by the jumper channel/waste channel intersection I and thejumper channel 170, reaches the waste channel 150. The waste channel 150generates a force F_(w), that increases to a value proportional to theline of contact between the blood and the hydrophilic surface, whichfirst pulls additional blood remaining in the receptor-inlet 161 intothe waste channel 150. As the waste channel 150 fills with excess bloodsample BLD, dead air disposed therein and displaced by the incomingblood BLD is vented to the external environment through the wastechannel venting aperture 151. Once the remaining blood sample drawn offfrom the receptor-inlet 161, force F_(w)+F_(p) becomes greater thanF_(s), and therefore, the leading edge E of the blood BLD in thesampling channel 130 starts pulling back towards the vent channel 180.

The leading edge E of the blood BLD in the sampling channel 130continues to be pulled back by force F_(w)+F_(p) and uncovers theoptical sensor 250. The volume of the blood sample BLD disposed in thesampling channel 130 at the moment the optical sensor 250 is uncovered,is the requisite volume. Consequently, the pump module 210 of the clotdetection instrument 200 is immediately activated by the uncoveredoptical sensor 250 and draws this requisite volume of blood sample BLDinto the test channels 140 such that the blood sample BLD is disposed inthe sections of the test channels 140 that are textured. The ratio offorce F_(w) to force F_(s) determines the sample pull back speed.Generally, a wider waste channel 150 has stronger pull back. In one,non-limiting embodiment, the ratio of force F_(w) to force F_(s) equals1.2. One of ordinary skill in the art will recognize that the forcesdescribed above may be adjusted by the material properties of thecuvette body 110, substrate 120, size and/or geometry of the pluralityof channels. The blood sample over shoot and pull back functions of thesampling channel 130 may also be adjusted and controlled by the volumeof dead air in the tubes 230 and pump module 210 of the clot detectioninstrument 200.

The automatic blood clot testing function of the cuvette 100 will now bedescribed in greater detail with reference to FIGS. 3A and 5. After thepump module 210 has drawn the blood sample into one or more testchannels 140 of the cuvette 100, the pump module 210 automaticallyswitches into a pumping mode where it alternately creates positive andnegative pressures in the test channels 140 of the cuvette 100. Thealternating positive and negative pressures (pumping pressure)reciprocally moves the blood samples BLD back and forth across texturedsections (or restricted areas) of the one or more test channels 140,thereby mixing the blood sample with dehydrated reagent, as shown inFIG. 3A. As the reagent rehydrates and mixes with the blood sample BLD,it triggers and accelerates the blood clotting cascade. Fibrin formationwithin the blood sample BLD causes the viscosity of the blood sample BLDto increase with time. The viscosity increase may be detected, in oneembodiment, by measuring the pumping pressure within each test channel140 over time. As shown in the graph of FIG. 5, the pumping pressurestarts at an initial pumping pressure value (pumping pressure baselineΔP_(baseline)) and increases with time, as the viscosity of the bloodincreases during clotting. The pressure sensors 240 of the blood clotdetection instrument 200, measure the pump pressure over time and theCPU 260 of the clot detection instrument 200 compares this data to theinitial pressure baseline ΔP_(baseline). The clotting time of the bloodsample may be determined when pressure value is greater than or equal toa preset threshold. In one embodiment, the clotting time is,

ΔP _(end point) −ΔP _(baseline)≧threshold,

where ΔP_(end point) is the clotting end point peak to peak pressure.

The preset threshold may be fixed or dynamic. In one embodiment, adynamic threshold may be,

ΔP _(baseline)+(0.3×ΔP _(baseline)).

In general, the hydrophilicity of the one or more test channels 140 willaid the robust automatic volumetric blood sample filling function of thecuvette 100, while impeding the clotting performance of the cuvette 100.Appropriately balancing the test channel 140 dimensions, geometry,degree of texturing/restriction size, and the hydrophilic properties ofthe cuvette body 110 and substrate 120, will provide the cuvette 100with requisite blood clotting performance.

The pump profile of the pump module 210, i.e., pumping speed and stroke,may also affect clotting performance. For example, a pump speed greaterthan 20 millisecond (ms) per pump step, equivalent to 20 ul per sec intest channel or a pump stroke greater than 55 steps, equivalent to0.044, may increase the chance of deforming a weak clot (InternationalNormalized Ratio>4.0), which may in turn, result in lower clot detectionprecision. In one embodiment, the pump profile is 40 ms per pump stepand 36 steps per pump direction (generates positive and negativepressures).

While exemplary drawings and specific embodiments have been describedand illustrated, it is to be understood that that the scope of thepresent invention is not to be limited to the particular embodimentsdiscussed. Thus, the embodiments shall be regarded as illustrativerather than restrictive, and it should be understood that variations maybe made in those embodiments by workers skilled in the art withoutdeparting from the scope of the present invention as set forth in theclaims that follow and their structural and functional equivalents.

1. A cuvette with a self-filling sample channel for use with a bloodclot detection instrument, the cuvette comprising: a main bodyincluding: a blood sample receptor-inlet; a channel arrangementcomprising: at least one test channel for performing a blood clottingtime measurement; a sampling channel communicating with the blood samplereceptor-inlet and the at least one test channel at least the samplingchannel having a hydrophilic surface portion; and a waste channelcommunicating with the sampling channel through a restriction, therestriction having a smaller cross sectional area than the samplechannel and the waste channel; and a vent opening communicating with thesampling channel, the vent opening located between the at least one testchannel and the restriction, wherein the sampling channel, the ventopening and the waste channel are configured to automatically draw arequisite volume of a blood sample deposited at the bloodreceptor-inlet, into the sampling channel, whereby the hydrophilicsurface portion of the sampling channel draws blood form the samplereceptor-inlet into the sampling channel, the vent opening vents airfrom the sampling channel as the sampling channel automatically fillswith blood, and the restriction delays filling of the waste channeluntil the requisite volume of blood has filled the sample channel. 2.(canceled)
 3. The cuvette of claim 1, wherein the channel arrangementfurther comprises a vent channel connecting the vent opening with thesampling channel.
 4. (canceled)
 5. The cuvette of claim 1, wherein thechannel arrangement is formed in a surface of the main body.
 6. Thecuvette of claim 5, further comprising a substrate for closing andsealing at least a portion of the channel arrangement formed in thesurface of the main body.
 7. The cuvette of claim 6, wherein thesubstrate forms the at least one surface portion of the sampling channelthat is hydrophilic.
 8. The cuvette of claim 6, wherein the substratecomprises a film with a hydrophilic surface, the hydrophilic surface ofthe substrate forming the at least one surface portion of the samplingchannel that is hydrophilic.
 9. The cuvette of claim 6, wherein thesubstrate comprises a film and a layer of hydrophilic material disposedon the film, the hydrophilic material forming the at least one surfaceportion of the sampling channel that is hydrophilic.
 10. The cuvette ofclaim 9, wherein the hydrophilic material is an adhesive which attachesthe substrate to the main body.
 11. The cuvette of claim 1, furthercomprising a blood clotting reagent disposed in the at least one testchannel.
 12. The cuvette of claim 1, wherein the at least one testchannel includes a section having at least one textured surface.
 13. Thecuvette of claim 1, wherein the at least one test channel includes arestriction.
 14. The cuvette of claim 1, wherein the main body is madeof one of a hydrophobic material, a hydrophilic material, or acombination of a hydrophobic material and a hydrophilic material. 15.The cuvette claim 1, wherein the waste channel has at least one surfaceportion, a coating, an insert or liner, and any combination thereof,that is hydrophilic.
 16. The cuvette of claim 1, wherein the at leastone test channel has at least one surface portion, a coating, an insertor liner, and any combination thereof, that is hydrophilic orhydrophobic.
 17. The cuvette of claim 3, wherein the vent channel has atleast one surface portion, a coating, an insert or liner, and anycombination thereof, that is hydrophilic.
 18. The cuvette of claim 1,wherein the restriction comprises a jumper channel or a restriction. 19.The cuvette of claim 18, wherein the jumper channel or the restrictionhas at least one surface portion, a coating, an insert or liner, and anycombination thereof, that is hydrophilic.
 20. (canceled)
 21. Anapparatus for measuring blood clotting time, the apparatus comprising:A) a blood clot detection instrument, the blood clot detectioninstrument comprising: a pump module; and at least one pressure sensor;and B) a cuvette with a self-filling sample channel for use with theblood clot detection instrument, the cuvette comprising: a main bodyincluding: i) a blood sample receptor-inlet; ii) a channel arrangementcomprising: a) at least one test channel for communicating, with thepump module when the cuvette is operatively coupled to the clotdetection instrument; b) a sampling channel communicating with the bloodsample receptor-inlet and the at least one test channel, at least thesampling channel having a hydrophilic surface portion; and c) a wastechannel communicating with the sampling channel through a restriction,the restriction having a smaller cross sectional area than the samplechannel and the waste channel; and iii) a vent opening communicatingwith the sampling channel, the vent opening located between the at leastone test channel and the restriction, wherein compressed air within theblood clot detection instrument and the at least one test channel, thesampling channel, the vent opening and waste channel, are configured toautomatically draw a requisite volume of a blood sample deposited at theblood receptor-inlet, into the sampling channel, and wherein the atleast one test channel of the cuvette, and the pump module and the atleast one pressure sensor of the clot detection instrument, coact toperform a blood clotting time measurement on the requisite volume of theblood sample, whereby the hydrophilic surface portion of the samplingchannel draws blood from the sample receptor-inlet into the samplingchannel, the vent opening vents air from the sampling channel as thesampling channel automatically fills with blood, and the restrictiondelays filling of the waste channel until the requisite volume of bloodhas filled the sample channel.
 22. (canceled)
 23. The apparatus of claim21, wherein the channel arrangement further comprises a vent channelconnecting the vent opening with the sampling channel.
 24. (canceled)25. The apparatus of claim 21, wherein the channel arrangement is formedin a surface of the main body.
 26. The apparatus of claim 25, furthercomprising a substrate for closing and sealing at least a portion of thechannel arrangement formed in the surface of the main body.
 27. Theapparatus of claim 26, wherein the substrate forms the at least onesurface portion of the sampling channel that is hydrophilic.
 28. Theapparatus of claim 26, wherein the substrate comprises a film with ahydrophilic surface, the hydrophilic surface of the substrate formingthe at least one surface portion of the sampling channel that ishydrophilic.
 29. The apparatus of claim 26, wherein the substratecomprises a film and a layer of hydrophilic material disposed on thefilm, the hydrophilic material forming the at least one surface portionof the sampling channel that is hydrophilic.
 30. The apparatus of claim29, wherein the hydrophilic material is an adhesive which attaches thesubstrate to the main body.
 31. The apparatus of claim 21, furthercomprising a blood clotting reagent disposed in the at least one testchannel.
 32. The apparatus of claim 21, wherein the at least one testchannel includes a section having at least one textured surface.
 33. Theapparatus of claim 21, wherein the at least one test channel includes arestriction.
 34. The apparatus of claim 21, wherein the main body ismade of one of a hydrophobic material, a hydrophilic material, or acombination of a hydrophobic material and a hydrophilic material. 35.The apparatus of claim 21, wherein the waste channel has at least onesurface portion, a coating, an insert or liner, and any combinationthereof, that is hydrophilic.
 36. The apparatus of claim 21, wherein theat least one test channel has at least one surface portion, a coating,an insert or liner, and any combination thereof, that is hydrophilic orhydrophobic.
 37. The apparatus of claim 23, wherein the vent channel hasat least one surface portion, a coating, an insert or liner, and anycombination thereof, that is hydrophilic.
 38. The apparatus of claim 21,wherein the restriction comprises a jumper channel or a restriction. 39.The apparatus of claim 38, wherein the jumper channel or restriction hasat least one surface portion, a coating, an insert or liner, and anycombination thereof, that is hydrophilic. 40-44. (canceled)
 45. Thecuvette of claim 1, wherein the main body comprises three test channelsin parallel communication with the sampling channel, a reagent disposedin each test channel.
 46. The cuvette of claim 45, wherein the reagentsare all the same, different, or combinations thereof.
 47. The apparatusof claim 21, wherein the main body comprises three test channels inparallel communication with the sampling channel, a reagent disposed ineach test channel.
 48. The apparatus of claim 47, wherein the reagentsare all the same, different, or combinations thereof.
 49. The apparatusof claim 21, wherein air compressed within the blood clot detectioninstrument, the at least one test channel of the cuvette, and thesection of the sampling channel extending beyond the vent opening of thecuvette, coacts with the waste channel to cause a leading edge of theblood sample drawn into the sampling channel from the bloodreceptor-inlet, to pull back within the sampling channel and uncover anoptical sensor of the blood clot detection instrument, the volume of theblood sample in the sampling channel at the time when the blood sampleis pulled back to uncover the optical sensor, equaling the requisitevolume, the uncovering of the optical sensor activating the pump moduleof the blood clot detection instrument, which draws the requisite volumeof the blood sample into the at least one test channel.
 50. The cuvetteof claim 1, further comprising: a first substrate with hydrophilicproperties for closing and sealing the sampling channel and the wastechannel; and a second substrate with hydrophobic properties for closingand sealing the at least one test channel.
 51. The cuvette of claim 50,wherein the sampling channel and the waste channel are formed in a firstsurface of the cuvette and the first substrate is affixed to the firstsurface, and the at least one test channel is formed in second surfaceof the cuvette and the second substrate is affixed to the secondsurface.
 52. The cuvette of claim 51, wherein the first and secondsurfaces are opposed to one another.
 53. The cuvette of claim 50,wherein the channel arrangement further comprises: a vent channelconnecting the vent opening with sampling channel, wherein the firstsubstrate closes and seals the vent channel and the jumper channel. 54.The apparatus of claim 21, further comprising; a first substrate withhydrophilic properties for closing and sealing the sampling channel andthe waste channel; and a second substrate with hydrophobic propertiesfor closing and sealing the at least one test channel.
 55. The apparatusof claim 54, wherein the sampling channel and the waste channel areformed in a first surface of the cuvette and the first substrate isaffixed to the first surface, and the at least one test channel isformed in second surface of the cuvette and the second substrate isaffixed to the second surface.
 56. The apparatus of claim 55, whereinthe first and second surfaces are opposed to one another.
 57. Theapparatus of claim 54, wherein the channel arrangement furthercomprises: a vent channel connecting the vent opening with samplingchannel, wherein the first substrate closes and seals the vent channeland the jumper channel.
 58. The cuvette of claim 1, wherein thehydrophilic surface is a coating, an insert, a liner, the material fromwhich the main body is made, and any combination thereof.
 59. Thecuvette of claim 3, wherein the sampling channel has a largercross-section than the vent channel.
 60. The cuvette of claim 20,wherein the sampling channel has a larger cross-section than the jumperchannel.
 61. The cuvette of claim 61, wherein the waste channel has alarger cross-section than the jumper channel.